The Vibrio parahaemolyticus Vp5 carrying pirA and pirB toxin genes cause hepatopancreatic necrosis disease (AHPND) in Pacific white shrimp culture, significantly decreasing shrimp production. The use of probiotic strain based on host-associated probiotic approach is a promising strategy to prevent vibriosis in shrimp culture. Under the laboratory trial, we evaluated the effect of indigenous probiotics Shewanella algae A3 and Serratia marcescens Van80 UB3 on immunity, histopathology, gene expression, and its protection against pathogen V. parahaemolyticus Vp5 of Pacific white shrimp (2 ± 0.5 g) by a 30-day feeding experiment. Five treatment groups using 150 shrimp of post larvae-10 (PL-10) including 106 cfu/g single indigenous probiotic A (Shewanella algae A3), 106 cfu/g single indigenous probiotic B (Serratia marcescens Van80 UB3), 106 cfu/g multi indigenous probiotic C (mix equal portion of Shewanella algae A3 and Serratia marcescens Van80 UB3), common feeding without infection (positive control), and common feeding (negative control) were designed. After 30 days of feeding trial, the shrimp were challenged with V. parahaemolyticus Vp5 and survival percentage was recorded for 14 days. As a result, Pacific white shrimp showed a significant (P < 0.05) higher survival rate in juvenile treated with the multi indigenous probiotics 95.83 ± 1.44% compared to control negative 72.22 ± 1.57%. Gene expression-related immunity in the intestine, muscle, hemolymph, and hepatopancreas including proPO and serine protease, and cathepsine L in multi indigenous probiotic C was increased significantly (P < 0.05) compared with A, B, and control group. Gene expression of cathepsine L- related muscle growth was significantly lowest in multi indigenous probiotic C group (P<0.05). Immune response parameters after 14-day challenge was higher in multi indigenous probiotic C group compared to the other groups. Histological analysis of the intestine and hepatopancreas indicated that probiotic supplement treatment has better conditions of normal tissue than the negative control. Finally, the results strongly recommended enriched Pacific white shrimp diets with 106 living bacteria in mix equal to the portion of Shewanella algae A3 and Serratia marcescens Van80 UB3 per gram of diet.